Details

Autor(en) / Beteiligte

• Yamamoto, T
• Nair, P
• Davis, P
• Ma, S-W
• Navratilova, E
• Moye, S
• Tumati, S
• Lai, J
• Vanderah, T W
• Yamamura, H I
• Porreca, F
• Hruby, V J

Titel

Design, Synthesis, and Biological Evaluation of Novel Bifunctional C-Terminal-Modified Peptides for beta / mu Opioid Receptor Agonists and Neurokinin-1 Receptor Antagonists

Ist Teil von

• Journal of medicinal chemistry, 2007-06, Vol.50 (12), p.2779-2786

Erscheinungsjahr

2007

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• A series of bifunctional peptides that act as agonists for 8 and mu opioid receptors with 8 selectivity and as antagonist for neurokinin-1 (NK1) receptors were designed and synthesized for potential application as analgesics in various pain states. The peptides were characterized using radioligand binding assays and functional assays using cell membrane and animal tissue. Optimization was performed on the fifth residue which serves as an address moiety for both receptor recognitions. It had critical effects on both activities at beta / mu opioid receptors and NK1 receptors. Among the synthesized peptides, H-Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-O-3,5-Bzl(CF sub(3)) sub(2) (5) and H-Tyr-D-Ala-Gly-Phe-Nle-Pro-Leu-Trp-O-3,5-Bzl (CF sub(3)) sub(2) (7) had excellent agonist activity for both beta opioid and mu opioid receptors and excellent antagonist activity for NK1 receptors. These results indicate that the rational design of multifunctional ligands with opioid agonist and neurokinin-1 antagonist activities can be accomplished and may provide a new tool for treatment of chronic and several pain states.